increase of dao with a gluten free diet

4
8/20/2019 Increase of DAO With a Gluten Free Diet http://slidepdf.com/reader/full/increase-of-dao-with-a-gluten-free-diet 1/4 Gut, 1987, 28, SI, 131-134 Postheparin plasma diamine oxidase increases in patients with coeliac disease during gluten free diet L D AGOSTINO, B DANIELE, S PIGNATA, M V BARONE C CIACCI, R SOLLAZZO, AND G MAZZACCA From the Cattedra di Malattie dell Apparato Digerente, 2a Facoltai di Medicina, 80131 Napoli, Italy. SUMMARY An intravenous injection of heparin releases diamine oxidase  DAO) from villous tip enterocytes. In a previous study, we found that postheparin plasma DAO  PHD) values were significantly lower in patients with malabsorption syndrome and small bowel atrophy at jejunal biopsy than in normal subjects. In this study we performed the PHD test in 14 coeliac patients before and after three and six months of gluten free diet to show whether the enterocytes maturing processes induced by the diet joined with enhanced PHD values and to assess the clinical usefulness of this test. In all subjectsjejunal biopsy carried out after six months showed a partial but consistent histological recovery. The clinical status, xylosuria and daily faecal fat excretion improved progressively and there was a significant increase  p < 0O001) in mean PHD activity that reached the normal range after three months. After six months a further slight increase of the mean PHD value was recorded. These data indicate that PHD values rise together with the improved intestinal absorptive functions of coeliac patients on gluten free diet and that this test is a useful tool in monitoring recovery of the small bowel mucosa. Diamine oxidase  DAO) is an enzyme whose low plasma values are enhanced by an intravenous injection of heparin which releases the enzyme from the enterocytes of the villus tip. Diamine oxidase, which is not excreted in active form in urine and bile, is rapidly removed from plasma by liver uptake.2 Lower postheparin plasma DAO  PHD) values have been found in subjects with an overt malabsorption syndrome and histologically proven small bowel mucosa atrophy than in normal subjects,3 and a significant inverse correlation between PHD and faecal fat excretion was found.4 Coeliac disease, a clinical condition in which small bowel mucosa atrophy is reverted by gluten free diet, is an interesting human model of intestinal adapta- tion.5 The dramatic proliferative changes induced by gluten free diet determine a rapid reconstitution of the mature enterocytic mass ;6 these mucosal modifica- tions are only indirectly reflected by the currently available tests of intestinal function that assess the absorptive capability of the small bowel. The detec- tion in plasma of enhanced concentrations of DAO which directly mirrors the morphologic and func- tional integrity of the small bowel mucosa347 could Address for correspondence: Luciano D Agostino, MD, Divisione di Gastro- enterologia, 2a Facolta di Medicina, via S Pansini 5, 80131 Napoli, Italy. be useful in monitoring mucosa recovery in coeliac patients on gluten free diet. To this end we performed the PHD test, xylosuria and faecal fat excretion  the two most widely used tests of malabsorption) in subjects with coeliac disease before and during treatment. Methods PATIENTS Heparin 15000 IU) was injected into an antecubital ar m vein by intravenous bolus in 14 subjects  10 women and four men; mean age 42+ 17 years) with coeliac disease before and three and six months after starting gluten free diet. At the same time daily faecal fat excretion and xylosuria were carried out. In all cases diagnosis was made by histological examination of jejunal mucosa samples obtained by Crosby capsule. A control biopsy was carried out after six months of gluten free diet. In each subject morphometric evaluation of small bowel mucosa was done with a LEITZ ocular micrometer. The patients were referred to hospital because of clinical and laboratory signs of malabsorption syn- drome; these progressively reverted after the starting of the gluten free diet. Laboratory signs of altered 131

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Page 1: Increase of DAO With a Gluten Free Diet

8/20/2019 Increase of DAO With a Gluten Free Diet

http://slidepdf.com/reader/full/increase-of-dao-with-a-gluten-free-diet 1/4

G u t , 1 9 8 7 , 2 8 ,

S I , 1 3 1 - 1 3 4

P o s t h e p a r i n

p l a s m a

d i a m i n e

o x i d a s e

i n c r e a s e s i n

p a t i e n t s

w i t h

c o e l i a c

d i s e a s e

d u r i n g

g l u t e n

f r e e

d i e t

L

D AGOSTINO,

B

DANIELE,

S

PIGNATA, M

V BARONE

C

CIACCI,

R

SOLLAZZO,

AND

G MAZZACCA

F r o m

t h e

C a t t e d r a

d i M a l a t t i e

d e l l A p p a r a t o

D i g e r e n t e ,

2 a

F a c o l t a i d i

M e d i c i n a , 8 0 1 3 1 N a p o l i , I t a l y .

SUMMARY

An

i n t r a v e n o u s

i n j e c t i o n

o f

h e p a r i n

r e l e a s e s

d i a m i n e

o x i d a s e

 DAO)

f r o m

v i l l o u s t i p

e n t e r o c y t e s .

I n

a

p r e v i o u s s t u d y ,

we f o u n d t h a t

p o s t h e p a r i n p l a s m a

DAO

  P H D )

v a l u e s were

s i g n i f i c a n t l y

l o w e r

i n

p a t i e n t s

w i t h

m a l a b s o r p t i o n

s y n d r o m e

a n d s m a l l b o w e l

a t r o p h y a t

j e j u n a l

b i o p s y

t h a n

i n

n o r m a l

s u b j e c t s .

I n

t h i s

s t u d y

we

p e r f o r m e d t h e

PHD

t e s t

i n

1 4

c o e l i a c

p a t i e n t s

b e f o r e

a n d a f t e r t h r e e a n d s i x

m o n t h s

o f

g l u t e n

f r e e

d i e t

t o s h o w w h e t h e r

t h e

e n t e r o c y t e s m a t u r i n g

processes

i n d u c e d

b y

t h e

d i e t

j o i n e d w i t h

e n h a n c e d

PHD

v a l u e s

a n d

t o

a s s e s s

t h e

c l i n i c a l

u s e f u l n e s s

o f

t h i s

t e s t .

I n

a l l

s u b j e c t s j e j u n a l b i o p s y c a r r i e d o u t

a f t e r s i x

m o n t h s s h o w e d a

p a r t i a l b u t c o n s i s t e n t

h i s t o l o g i c a l recovery.

T h e c l i n i c a l s t a t u s ,

x y l o s u r i a a n d d a i l y

f a e c a l

f a t e x c r e t i o n i m p r o v e d

p r o g r e s s i v e l y

a n d t h e r e was a

s i g n i f i c a n t i n c r e a s e

  p

<

0 O 0 0 1 )

i n

mean

PHD

a c t i v i t y

t h a t r e a c h e d t h e

n o r m a l

range

a f t e r t h r e e

m o n t h s .

A f t e r s i x m o n t h s a

f u r t h e r s l i g h t i n c r e a s e o f t h e mean PHD v a l u e

was r e c o r d e d .

T h e s e

d a t a

i n d i c a t e t h a t

PHD

v a l u e s

r i s e t o g e t h e r w i t h

t h e

i m p r o v e d i n t e s t i n a l

a b s o r p t i v e

f u n c t i o n s o f c o e l i a c

p a t i e n t s

o n

g l u t e n

f r e e

d i e t a n d t h a t t h i s t e s t i s a u s e f u l t o o l

i n

m o n i t o r i n g recovery

o f t h e s m a l l b o w e l mucosa.

D i a m i n e o x i d a s e

  D A O )

i s a n

e n z y m e

w h o s e l o w

p l a s m a

v a l u e s a r e e n h a n c e d

b y

a n

i n t r a v e n o u s

i n j e c t i o n

o f

h e p a r i n

w h i c h

r e l e a s e s t h e

e n z y m e

f r o m

t h e

e n t e r o c y t e s

o f t h e v i l l u s

t i p .

D i a m i n e

o x i d a s e ,

w h i c h

i s n o t e x c r e t e d

i n

a c t i v e f o r m i n u r i n e

a n d

b i l e ,

i s

r a p i d l y

r e m o v e d

f r o m p l a s m a

b y

l i v e r

u p t a k e . 2

L o w e r

p o s t h e p a r i n p l a s m a

DAO

  P H D )

v a l u e s

h a v e

b e e n

f o u n d

i n

s u b j e c t s

w i t h a n o v e r t

m a l a b s o r p t i o n

s y n d r o m e

a n d

h i s t o l o g i c a l l y

p r o v e n

s m a l l b o w e l

m u c o s a

a t r o p h y

t h a n

i n

n o r m a l

s u b j e c t s , 3

a n d

a

s i g n i f i c a n t

i n v e r s e

c o r r e l a t i o n

b e t w e e n

PHD a n d

f a e c a l

f a t

e x c r e t i o n

w a s

f o u n d . 4

C o e l i a c

d i s e a s e ,

a c l i n i c a l c o n d i t i o n

i n w h i c h s m a l l

b o w e l m u c o s a

a t r o p h y

i s r e v e r t e d

b y

g l u t e n

f r e e

d i e t ,

i s a n

i n t e r e s t i n g

h u m a n m o d e l

o f

i n t e s t i n a l

a d a p t a -

t i o n . 5

T h e

d r a m a t i c

p r o l i f e r a t i v e

c h a n g e s

i n d u c e d

b y

g l u t e n

f r e e

d i e t

d e t e r m i n e a

r a p i d

r e c o n s t i t u t i o n

o f

t h e

m a t u r e

e n t e r o c y t i c

m a s s

; 6

t h e s e m u c o s a l m o d i f i c a -

t i o n s a r e o n l y

i n d i r e c t l y

r e f l e c t e d

b y

t h e

c u r r e n t l y

a v a i l a b l e

t e s t s

o f i n t e s t i n a l

f u n c t i o n

t h a t a s s e s s

t h e

a b s o r p t i v e

c a p a b i l i t y

o f t h e s m a l l b o w e l . T h e d e t e c -

t i o n

i n

p l a s m a

o f e n h a n c e d

c o n c e n t r a t i o n s o f DAO

w h i c h

d i r e c t l y

m i r r o r s t h e

m o r p h o l o g i c

a n d f u n c -

t i o n a l

i n t e g r i t y

o f

t h e

s m a l l b o w e l m u c o s a 3 4 7 c o u l d

A d d r e s s f o r

c o r r e s p o n d e n c e : L u c i a n o D A g o s t i n o ,

MD,

D i v i s i o n e

d i G a s t r o -

e n t e r o l o g i a ,

2 a F a c o l t a

d i

M e d i c i n a , v i a

S

P a n s i n i

5 , 8 0 1 3 1

N a p o l i , I t a l y .

b e

u s e f u l

i n

m o n i t o r i n g

m u c o s a

r e c o v e r y

i n

c o e l i a c

p a t i e n t s

o n

g l u t e n

f r e e

d i e t . To

t h i s

e n d w e p e r f o r m e d

t h e

PHD

t e s t ,

x y l o s u r i a

a n d

f a e c a l

f a t

e x c r e t i o n

  t h e

t w o m o s t

w i d e l y

u s e d

t e s t s

o f m a l a b s o r p t i o n ) i n

s u b j e c t s w i t h

c o e l i a c

d i s e a s e

b e f o r e

a n d

d u r i n g

t r e a t m e n t .

M e t h o d s

PATIENTS

H e p a r i n 1 5 00 0

I U )

w a s i n j e c t e d i n t o

a n

a n t e c u b i t a l

arm v e i n

b y

i n t r a v e n o u s b o l u s

i n

1 4

s u b j e c t s

  1 0

women

a n d

f o u r

m e n ;

mean

a g e 42+ 1 7 y e a r s )

w i t h

c o e l i a c

d i s e a s e b e f o r e a n d t h r e e a n d

s i x m o n t h s

a f t e r

s t a r t i n g g l u t e n

f r e e d i e t . A t

t h e

s a m e

t i m e

d a i l y

f a e c a l

f a t

e x c r e t i o n

a n d

x y l o s u r i a

w e r e

c a r r i e d

o u t .

I n

a l l

c a s e s

d i a g n o s i s

w a s

m a d e b y h i s t o l o g i c a l

e x a m i n a t i o n o f

j e j u n a l

m u c o s a

s a m p l e s o b t a i n e d b y

C r o s b y c a p s u l e .

A c o n t r o l

b i o p s y w a s c a r r i e d o u t

a f t e r

s i x m o n t h s

o f

g l u t e n

f r e e

d i e t .

I n

e a c h s u b j e c t

m o r p h o m e t r i c

e v a l u a t i o n o f

s m a l l b o w e l

m u c o s a

w a s

d o n e w i t h

a

LEITZ

o c u l a r

m i c r o m e t e r .

T h e

p a t i e n t s

w e r e

r e f e r r e d

t o

h o s p i t a l

b e c a u s e o f

c l i n i c a l

a n d

l a b o r a t o r y s i g n s

o f

m a l a b s o r p t i o n

s y n -

d r o m e ;

t h e s e

p r o g r e s s i v e l y

r e v e r t e d

a f t e r

t h e s t a r t i n g

o f t h e

g l u t e n

f r e e

d i e t .

L a b o r a t o r y

s i g n s

o f a l t e r e d

1 3 1

Page 2: Increase of DAO With a Gluten Free Diet

8/20/2019 Increase of DAO With a Gluten Free Diet

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D A g o s t i n o ,

D a n i e l e ,

P i g n a t a ,

B a r o n e ,

C i a c c i , S o l l a z z o ,

a n d

M a z z a c c a

l i v e r

f u n c t i o n w e r e

a b s e n t .

I n f o r m e d

c o n s e n t

w a s

o b t a i n e d f r o m

a l l

p a t i e n t s .

No

c o m p l i c a t i o n s

f r o m

t h e h e p a r i n

b o l u s

o r

j e j u n a l

b i o p s y

o c c u r r e d .

I n

a l l

s u b j e c t s

p a r t i a l

t h r o m b o p l a s t i n

t i m e

w a s

m o n i t o r e d

a n d

r e t u r n e d

t o

n o r m a l

v a l u e s

w i t h i n

f i v e

h o u r s

a f t e r

h e p a r i n

i n j e c t i o n .

DAO

ASSAY

B l o o d

s a m p l e s   4

m l )

w i t h d r a w n

b y

v e i n

c a t h e t e r

w e r e

c o l l e c t e d i n

h e p a r i n i s e d t u b e s

a t

0 , 5 ,

1 5 ,

3 0 , 4 5 ,

6 0 , 9 0 ,

1 2 0 m i n u t e s

a f t e r

t h e i v

h e p a r i n

b o l u s .

A l l

s a mp l e s w e r e

c e n t r i f u g e d

a t 3 0 0 0

g

a n d

t h e

p l a s m a

w a s

s t o r e d a t -20

°C

a n d

a s s a y e d

f o r

DAO w i t h i n

a

w e e k . D i a m i n e

o x i d a s e

a s s a y

w a s

d o n e

b y

t h e

O k u y a m a

a n d

K o b a y a s h i m e t h o d 8

a s

m o d i f i e d

i n

o u r

p r e v i o u s

s t u d y . 9

D i a m i n e o x i d a s e

a c t i v i t y

w a s

e x -

p r e s s e d a s

U / m l ( 1 U

=

 

nM

o f

p u t r e s c i n e

d i h y d r o -

c h l o r i d e

o x i d a t e d

i n

o n e

h o u r

a t

3 7

° C ,

pH

7

2 ) .

T h e

a r e a

u n d e r

t h e

DAO r e l e a s e

c u r v e s ,

e x p r e s s e d

a s

U / m l

- m i n ,

w a s

c a l c u l a t e d

b y

t r a p e z o i d

m e t h o d .

FAECAL

FAT

EXCRETION

P a t i e n t s r e c e i v e d

a

s t a n d a r d

h o s p i t a l

d i e t

c o n t a i n i n g

1 0 0

g f a t

d a i l y

d u r i n g t h e

t h r e e

d a y s

o f

f a e c e s

s a m p l i n g .

A

f a e c a l f a t

e x c r e t i o n ,

a s s a y e d

a c c o r d i n g

t o

V a n

d e r

K a m e r , 1 0

o f

l e s s

t h a n 7

g / d a y

w a s

t a k e n a s

n o r m a l .

D-XYLOSE

ABSORPTION TEST

D - x y l o s e

  2 5

g )

i n

2 5 0 m l

o f

w a t e r w a s

a d m i n i s t e r e d

t o

p a t i e n t s

t h e

m o r n i n g

a f t e r

a n

o v e r n i g h t

f a s t .

U r i n e

w a s

c o l l e c t e d f o r

f i v e

h o u r s .

An

e x c r e t i o n

o f 4

g

o r

m o r e w a s

c o n s i d e r e d

n o r m a l . T h e

a s s a y

w a s

c a r r i e d

o u t

a c c o r d i n g

t o

a

m o d i f i e d

m e t h o d 1

o f R o e

a n d

R i c e . 1 2

STATISTICAL

METHODS

S t a t i s t i c a l

e v a l u a t i o n

i n c l u d e s

a

t w o - t a i l e d

u n p a i r e d

S t u d e n t s t

t e s t .

R e s u l t s ,

e x p r e s s e d a s

m e a n

+

S D ,

w e r e

c o n s i d e r e d

s i g n i f i c a n t

w h e n

p <

0 0 5 .

R e s u l t s

P o s t h e p a r i n

p l a s m a

v a l u e s

i n

1 4

p a t i e n t s w i t h

c o e l i a c

d i s e a s e

b e f o r e

a n d

a f t e r

t h r e e

a n d

s i x

m o n t h s

o f

g l u t e n

f r e e

d i e t

a r e s h o w n i n

F i g u r e

1 .

I n c r e a s e d m e a n

PH D

v a l u e s ,

r e a c h i n g t h e

n o r m a l

r a n g e , w e r e

p r e s e n t

a f t e r

t h r e e

m o n t h s ;

a f t e r

s i x

m o n t h s

a

f u r t h e r s l i g h t

i n c r e a s e o f

t h e s e

v a l u e s

w a s

r e c o r d e d .

Mean

+

SD

PH D

a r e a

v a l u e s

  F i g . 2 )

w e r e

1 9 5

+ 9 4

o n

d i a g n o s i s

a n d

4 1 1

+

1 1 9

a n d

4 9 3

+

1 1 0

  p

<

0 0 0 1 ;

n o r m a l

v a l u e s

m o r e

t h a n

3 7 0 )

a f t e r

t h r e e

a n d

s i x

m o n t h s

o f

t r e a t m e n t

r e s p e c t i v e l y .

T h e

t e s t

w a s a l s o

u n d e r t a k e n

i n

f i v e

p a t i e n t s a f t e r

o n l y

1 0

d a y s

o f

d i e t ; a

s i g n i f i c a n t

i n c r e a s e

i n

PH D

v a l u e s

w a s

r e c o r d e d i n

t h r e e o f t h e s e .

D a i l y

f a e c a l f a t

7 -

6 .

 

2,

1 5

O O O I U o f

h e p o r i n

v

 

6

  U n t N

~

0

4 m 5

6 0

T i m e .

(

m r n J

9 0

1 2 0

F i g .

 

P o s t h e p a r i n

DAO r e l e a s e

c u r v e s i n

1 4

s u b j e c t s

w i t h

c o e l i a c

d i s e a s e

b e f o r e

a n d

d u r i n g g l u t e n

f r e e

d i e t .

S h a d e d

a r e a

r e p r e s e n t s

t h e

n o r m a l

r a n g e .

7 0 0

6

n

0 0

 

2 0 0 -

0

3

6

T i m e

  m o n t h s )

F i g .

2

P o s t h e p a r i n

DAO

a r e a

v a l u e s i n

1 4

s u b j e c t s

w i t h

c o e l i a c

d i s e a s e

b e f o r e

a n d

d u r i n g

g l u t e n

f r e e d i e t .

S h a d e d

a r e a

r e p r e s e n t s

t h e

n o r m a l

r a n g e .

e x c r e t i o n ,

x y l o s u r i a

a n d

m o r p h o m e t r i c

d a t a

a r e

s h o w n

i n

t h e

T a b l e .

D a i l y

f a e c a l

f a t

e x c r e t i o n

p r o g r e s s i v e l y

d e c r e a s e d

a n d

x y l o s u r i a

i n c r e a s e d

d u r i n g t r e a t m e n t . T h e

h i s t o -

l o g i c a l

e v a l u a t i o n

o f

j e j u n a l s p e c i m e n s

a f t e r

s i x

1 3 2

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DAO i n t r e a t e d

c o e l i a c

s u b j e c t s

1 3 3

T a b l e C h a n g e s

i n d a i l y

f a e c a l

f a t

e x c r e t i o n , x y l o s u r i a ,

v i l l u s

h e i g h t

a n d

c r y p t h e i g h t

i n 1 4 s u b j e c t s b e f o r e a n d

d u r i n g

g l u t e n f r e e

d i e t .

M o n t h s

0

3

6

F a e c a l f a t

e x c r e t i o n   g / d a y ) 2 7

± 9 1 3 ± 5 9

±

2

D - x y l o s e

e x c r e t i o n

( g )

2 - 7 1 3 - 8

±

4 - 2

1 8

V i l l u s

h e i g h t

( , s m )

3 5 ± 3

2 5 5

± 1 0 5

C r y p t h e i g h t

  , a m )

3 2 8 ± 2 8

1 6 7 ±

6 3

m o n t h s

o f

d i e t

s h o w e d

a n i n c o m p l e t e

n o r m a l i s a t i o n

o f

v i l l u s

m o r p h o l o g y

i n

a l l

p a t i e n t s .

D i s c u s s i o n

T h i s s t u d y s h o w s

t h a t

i n

p a t i e n t s

w i t h

c o e l i a c

d i s e a s e

o n

g l u t e n

f r e e d i e t t h e f u n c t i o n a l r e c o v e r y

o f

s m a l l

b o w e l

m u c o s a c l o s e l y

a c c o m p a n i e s

t h e

r a p i d

n o r m a l -

i s a t i o n

o f t h e

PH D

t e s t .

D i a m i n e o x i d a s e

i s a n

e n z y m e

l o c a t e d

i n v i l l u s

t i p

e n t e r o c y t e s

o f mam-

m a l i a n s

a n d

i t s

a c t i v i t y

i n c r e a s e s

s u c c e s s i v e l y

f r o m

t h e

d u o d e n u m

t o

t h e

i l e u m . 9

1 3 T h i s

e n z y m e

f u n c t i o n s

a s

a p l a s m a

m a r k e r

o f s m a l l

b o w e l

m u c o s a m a t u r a -

t i o n

a n d

i n t e g r i t y 4

a n d

i n j u r y

a n d

r e c o v e r y

i n t h e

r a t . 5 H e p a r i n

i n d u c e s h i g h

DAO c o n c e n t r a t i o n s

i n

p l a s m a

b y

r e l e a s i n g

t h e e n z y m e

f r o m d i f f e r e n t i a t e d

a n d

n o n - r e p l i c a t i n g e n t e r o c y t e s .

P a t i e n t s

w i t h

s m a l l

b o w e l

m u c o s a

a t r o p h y

a n d m a la b s o r p t i o n s y n d r o m e

p r e s e n t e d

PH D v a l u e s

s i g n i f i c a n t l y

l o w e r

t h a n

d i d

n o r m a l s u b j e c t s . P o s t h e p a r i n

a r e a

v a l u e s

i n

t h e s e

p a t i e n t s

w e r e

a l s o i n v e r s e l y

c o r r e l a t e d

w i t h t h e

d a i l y

f a e c a l f a t

e x c r e t i o n ,

i n d i c a t i n g

t h a t

PH D

t e s t e x p l o r e s

t h e r e m a i n i n g

m a t u r e

e n t e r o c y t i c

m a s s . 4

T h e s e

d a t a i n d u c e d

u s t o i n v e s t i g a t e

w h e t h e r

e n t e r o c y t e

m a t u r i n g

p r o c e s s e s

d e t e r m i n e d b y g l u t e n

f r e e d i e t w e r e c o n n e c t e d

w i t h

i n c r e a s e d a m o u n t s o f

r e l e a s a b l e i n t e s t i n a l

DAO

i n

c o e l i a c p a t i e n t s

a n d

t o

a s s e s s

t h e

u s e f u l n e s s

o f

t h i s t e s t

i n

m o n i t o r i n g

s m a l l

b o w e l m u c o s a

r e c o v e r y .

T h e , r e s u l t s

s h o w

t h a t

t h r e e

m o n t h s

a f t e r s t a r t i n g

t r e a t m e n t m e a n

PHD

v a l u e s r e a c h e d

t h e n o r m a l

r a n g e

a n d t h a t

n o r m a l

v a l u e s

w e r e r e c o r d e d

a t

t h e s i x

m o n t h e v a l u a t i o n .

I t

i s

a l s o i n t e r e s t i n g t h a t t h e

e a r l y

c l i n i c a l i m p r o v e m e n t

i n d u c e d b y

a

f e w d a y s o f

g l u t e n

f r e e

d i e t w a s

a s s o c i a t e d

w i t h a

s i g n i f i c a n t i n c r e a s e

i n

PHD

v a l u e s

i n t h r e e s u b j e c t s .

T h e a b s o r p t i o n t e s t s

p e r f o r m e d

a f t e r t h r e e a n d

s i x m o n t h s s h o w e d

a

p r o g r e s s i v e

i m p r o v e m e n t ,

a n d a t s i x m o n t h s q u i t e

c o m p l e t e

n o r m a l i s a t i o n o f s m a l l i n t e s t i n a l

a b s o r p t i v e

f u n c t i o n s ,

a l t h o u g h

t h e

h i s t o l o g i c a l

p i c t u r e

o f j e j u n a l

s p e c i m e n s

o n l y p a r t i a l l y

i m p r o v e d .

T h e s e

f i n d i n g s

a r e

c o n s i s t e n t

w i t h

t h e

o b s e r v a t i o n t h a t

i n

c o e l i a c

p a t i e n t s

o n

g l u t e n

f r e e

d i e t

t h e

m u c o s a o f t h e d i s t a l

s m a l l

i n t e s t i n e

i m p r o v e s m o r e

r a p i d l y

t h a n

t h a t

o f

t h e

s e v e r e l y

i n v o l v e d p r o x i m a l b o w e l 6 a n d w i t h

t h e

p r e v a l e n t l y

d i s t a l

l o c a t i o n

o f DAO a l o n g

t h e

s m a l l

b o w e l . 9

1 3

T h e

e a r l y i n c r e a s e

i n

r e l e a s e

o f e n t e r o c i t i c

DAO

may

d e p e n d u p o n

t h e

r a p i d

m a t u r i n g

p r o c e s s e s

i n d u c e d b y

g l u t e n

f r e e d i e t . I n

f a c t , t h e

d i e t i n d u c e s

t h e

  f l a t c o e l i a c

m u c o s a ,

t h a t

s h o w s a

t h r e e - f o l d

i n c r e a s e

i n

t h e

s i z e

o f

t h e

p r o l i f e r a t i o n

c o m p a r t m e n t

c o m p a r e d w i t h n o r m a l a n d a n e t s i x - f o l d

i n c r e a s e

i n

c r y p t

c e l l

p r o d u c t i o n

r a t e , 5

t o

s h i f t t o a

n o r m a l

r e p l i c a t i v e

p a t t e r n w i t h a

p r o g r e s s i v e

i n c r e a s e i n

t h e

n u m b e r o f t h e m a t u r e

e n t e r o c y t e s .

I n

c o n c l u s i o n , t h e s e

d a t a

s u g g e s t t h a t

i n

p a t i e n t s

w i t h

c o e l i a c d i s e a s e

t h e

f u n c t i o n a l r e c o v e r y o f

t h e

s m a l l

b o w e l m u c o s a ,

r e v e a l e d

b y

c l i n i c a l

i m p r o v e m e n t

a n d

n e a r - n o r m a l i s a t i o n

o f

a b s o r p t i v e

t e s t s

i s

c l o s e l y

a s s o c i a t e d

w i t h

h i g h

PH D v a l u e s .

F u r t h e r m o r e ,

t h e

m a t u r i n g

p r o c e s s e s

t h a t

b e g i n

w i t h i n a f e w

d a y s o f

g l u t e n

f r e e

d i e t , a r e

c l e a r l y s h o w n b y

i n c r e a s e d

PH D

v a l u e s . F o r

t h e a b o v e r e a s o n s

t h i s

t e s t , c a r r i e d o u t i n

man

f o r

t h e f i r s t

t i m e

b y U S , 3

a p p e a r s

t o

b e

a u s e f u l

t o o l

i n

t h e

e a r l y

m o n i t o r i n g

o f s m a l l

b o w e l m u c o s a

r e c o v e r y .

T h e a u t h o r s t h a n k D r s

F

S a b b a t i n i

a n d A

D A r i e n z o

f o r

e n c o u r a g e m e n t

a n d

M r

P

E s p o s i t o

f o r t e c h n i c a l

a s s i s t a n c e . T h i s

w o r k

w a s

s u p p o r t e d

i n

p a r t b y

a

g r a n t

f r o m

M i n i s t e r o

P u b b l i c a

I s t r u z i o n e .

P r e s e n t e d

i n

p a r t

a t t h e

P o s t e r s e s s i o n o f

t h e I t a l i a n

S o c i e t y o f

G a s t r o e n t e r o l o g y   S I G E )

m e e t i n g ,

M i l a n , N o v e m b e r

1 4 - 1 6 , 1 9 8 5 a n d

p u b l i s h e d

i n

a b s t r a c t f o r m i n

I t a l

J

G a s t r o e n t e r o l

1 9 8 6 ;

1 8 : 6 1 .

R e f e r e n c e s

  S h a k i r

KMM,

M a r g o l i s

S ,

B a y l i n

S B

L o c a l i z a t i o n o f

h i s t a m i n a s e

  D i a m i n e

o x i d a s e )

i n

r a t

s m a l l

b o w e l

i n t e s t i n a l

m u c o s a :

s i t e

o f r e l e a s e

b y h e p a r i n . B i o c h e m

P h a r m a c o l

1 9 7 7 ;

2 6 :

2 3 4 3 - 7 .

2

D A g o s t i n o

L ,

C i a c c i

C ,

C a p u a n o

G , e t a l .

M e t a b o l i c

f a t e

o f

p l a s m a D i a m i n e

o x i d a s e : e v i d e n c e o f

i s o l a t e d a n d

p e r f u s e d

r a t

l i v e r

u p t a k e .

D i g e s t i o n 1 9 8 6 ;

3 4 :

2 4 3 - 5 0 .

3

D A g o s t i n o

L ,

C i a c c i

C , D a n i e l e

B , B a r o n e

MV,

S o l l a z z o

R ,

M a z z a c c a

G .

P l a s m a

D i a m i n e

o x i d a s e

 DAO)

a n d

h e p a r i n .

[ L e t t e r ] .

D i g

D i s

S c i 1 9 8 4 ; 2 9 :

1 0 7 0 - 1 .

4

D A g o s t i n o

L ,

C i a c c i

C ,

D a n i e l e

B ,

B a r o n e MV,

S o l l a z z o

R ,

M a z z a c c a

G .

P o s t h e p a r i n p l a s m a

D i a m i n e

o x i d a s e i n

s u b j e c t s w i t h

s m a l l

b o w e l

m u c o s a

a t r o p h y .

D i g

D i s

S c i

1 9 8 7 ;

3 2 : 3 1 3 - 1 7 .

5

W a t s o n

A J , A p p l e t o n

DR, W r i g h t

NA. A d a p t i v e

c e l l -

p r o l i f e r a t i v e

c h a n g e s

i n

t h e s m a l l

i n t e s t i n a l

m u c o s a

i n

c o e l i a c d i s e a s e .

I n :

P o l a k

J M , B l o o m

S R ,

W r i g h t

NA,

D a l y M J ,

e d s .

S t r u c t u r e o f t h e g u t .

W a r e ,

H e r t s : G l a x o

G r o u p

R e s e a r c h

L t d ,

1 9 8 2 :

4 3 1 - 4 3 .

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1 3 4

D A g o s t i n o , D a n i e l e ,

P i g n a t a , B a r o n e ,

C i a c c i , S o l l a z z o ,

a n d

M a z z a c c a

6

M a c D o n a l d WC, B r a n d b o r g

L L ,

F l i c k

A L ,

T r i e r

J S ,

R u b i n

C E .

S t u d i e s o f

c e l i a c s p r u e .

I V . T h e

r e s p o n s e

o f

t h e w h o l e

l e n g t h

o f

t h e

s m a l l b o w e l

t o

a

g l u t e n - f r e e

d i e t .

G a s t r o e n t e r o l o g y 1 9 6 4 ;

4 7 :

5 7 3 .

7 L u k

GD,

B a y l e s s TM ,

B a y l i n S B .

P l a s m a

p o s t h e p a r i n

D i a m i n e

o x i d a s e . S e n s i t i v e

p r o v o c a t i v e

t e s t

f o r

q u a n t i -

t a t i n g l e n g t h o f

a c u t e i n t e s t i n a l

m u c o s a l

i n j u r y i n

t h e

r a t .

J C l i n

I n v e s t

1 9 8 3 ;

7 1 :

1 3 0 8 - 1 5 .

8

O k u y a m a T , K o b a y a s h i

Y .

D e t e r m i n a t i o n

o f D i a m i n e

o x i d a s e a c t i v i t y b y

l i q u i d

s c i n t i l l a t i o n

c o u n t i n g .

A r c h

B i o c h e m

B i o p h y s 1 9 6 1 ; 9 5 : 2 4 2 5 0

9

D A g o s t i n o L , D A r g e n i o G ,

C i a c c i C ,

D a n i e l e

B ,

M a c c h i a

V , M a z z a c c a

G .

D i a m i n e o x i d a s e i n r a t

s m a l l

b o w e l : d i s t r i b u t i o n

i n

d i f f e r e n t

s e g m e n t s

a n d c e l l u l a r

l o c a t i o n .

E n z y m e 1 9 8 4 ; 3 1 : 2 1 7 - 2 0 .

1 0

V a n d e r K a m e r

J H , H u i n i n k

H T B , W e i j e r s HA. R a p i d

m e t h o d f o r t h e

d e t e r m i n a t i o n o f

f a t

i n f e c e s .

J B i o l C h e m

1 9 4 9 ; 1 7 7 : 3 4 7 - 5 2 .

1 1

G o o d h a r t

J M ,

K i n s i n g t o n

G R .

M o d i f i c a t i o n s

o f

t h e

m e t h o d

f o r

t h e

e s t i m a t i o n o f

x y l o s e i n

u r i n e . J

C l i n

P a t h o l

1 9 6 8 ;

2 2 :

6 2 1 - 4 .

1 2

R o e J H ,

R i c e

EW. A

p h o t o m e t r i c

m e t h o d f o r

t h e

d e t e r m i n a t i o n

o f

f r e e

p e n t o s e s

i n

a n i m a l

t i s s u e s .

J

B i o l

C h e m

1 9 4 8 ;

1 7 3 :

5 0 7 - 1 2 .

1 3 B i e g a n u s k i

T .

B i o c h e m i c a l ,

p h y s i o l o g i c a l

a n d

p a t h o -

p h y s i o l o g i c a l

a s p e c t s o f

i n t e s t i n a l

D i a m i n e

o x i d a s e .

A c t a

P h y s i o l

P o l

1 9 8 3 ;

3 4 :

1 3 9 - 5 3 .

1 4

L u k

GD, B a y l e s s

TM , B a y l i n S B .

D i a m i n e

o x i d a s e

  D A O )

a

c i r c u l a t i n g

m a r k e r f o r

r a t m u c o s a l

m a t u r a t i o n

a n d

i n t e g r i t y .

J

C l i n

I n v e s t

1 9 8 0 ; 6 6 :

6 6 - 7 0 .

1 5 L u k

GD,

V a u g h a n

W P ,

B u r k e

P J ,

B a y l i n

S B .

D i a m i n e

o x i d a s e

a s a

p l a s m a m a r k e r

o f

r a t

i n t e s t i n a l

m u c o s a

i n j u r y

a n d

r e g e n e r a t i o n

a f t e r

a d m i n i s t r a t i o n o f

1 - B - D -

A r a b i n o f u r a n o s y l c y t o s i n e .

C a n c e r

R e s

1 9 8 1 ; 4 1 :

2 2 3 4 -

7 .